The objectives of our Harvard Pulmonary SCOR program are to generate new knowledge relating to the physiology, pharmacology, pathology, and epidemiology of chronic obstructive lung diseases and to apply this knowledge to new modalities of therapy and prevention. We intend to realize these objectives through a variety of approaches which range from studies of cells and tissues to those of whole animals and human populations. Through the organizational structure and financial support provided by the SCOR grant, we hope to increase the impact of our research on the prevention, diagnosis, and treatment of chronic obstructive lung diseases. A major goal is to facilitate productive interactions between basic and applied respiratory biology. In part this will be accomplished by fostering active collaborations of the Respiratory Biology Program at the Harvard School of Public Health with the Respiratory Divisions of the Brigham and Women's, Beth Israel, Children's and West Roxbury Veteran's Administration Hospitals. The proposed projects are: Project 1, Models of Chronic Airway Irritation; Project 2, Effects of Exercise and Increased Ventilation on Pulmonary Exposure and Responses; Project 3, Trunk Mechanics and Control; Project 4, Respiratory Perceptions from Lungs and Chemoreceptors; Project 5, Characterization and Mechanisms of Dyspnea; Project 6, Physiologic, Diagnostic, and Therapeutic Implications of Variations in Airway Size; Project 7, Role of Pulmonary Macrophages in Airway and Parenchymal Injury; Project 8, Prospective Evaluation of Airways Reactivity; Project 9, Experimental Design, Mathematical Modeling, and Statistical Analysis Core; and Project 10, Administrative Core.